Wettable powder compositions of ionophore antibiotics

ABSTRACT

A dry composition of an ionophore antibiotic such as monensin comprising from 10 to 95% (when expressed as the sodium salt) of at least one crystalline ionophore antibiotic, from 0 to 10% antifoam agent(s), from 0.1 to 20% wetting and/or surfactant agent(s),  
     from 0.1 to 10% dispersal agent(s), and from 0.1 to 20% suspension agent(s). The use of the composition is as a suspension in water alone or in conjunction with a milk replacer composition and/or a milk extender composition in water as a calf feed composition.

TECHNICAL FIELD

[0001] The present invention relates to wettable powder compositions ofan ionophore antibiotic useful as a feed supplement to a ruminant animal(including a suckling ruminant juvenile animal), methods of using such acomposition in conjunction with milk and/or milk replacement powders andas a milk replacer for such ruminant animals and related means andmethods.

BACKGROUND ART

[0002] In U.S. Pat. No. 3839557 of Eli Lilly and Company (the fullcontent of which is hereby here incorporated by reference) there isdisclosure of a method of increasing the efficiency of feed utilisationby ruminant animals having a developed rumen function where anantibiotic chosen from the group A204 (U.S. Pat. No. 3,705,238)dianemycin (fermentation product of Streptomyces Hygroscopicus NRRL3444) monensin (U.S. Pat. No. 501,358), X537A (Netherlands patent70.12,108) nigericin (U.S. Pat. No. 3,555,150) and X206 (1951, Berger etal, J. Am. Chem. Soc. 73, 5295-98 (1951)), and certain derivativesthereof, are orally administered to the ruminant animals whose feedefficiency is to be increased.

[0003] Examples of appropriate ruminant animals given are cattle, sheepand goats.

[0004] The invention of U.S. Pat. No. 3,839,557 is indicated as beinguseful to ruminants which have a developed rumen function. Youngruminants (basically those still unweaned) are stated as functioning asmonogastric animals and that it is not until such young ruminant eatsolid feed containing cellulose, starch and other carbohydrates that thefunction of the rumen begins to develop and the microbiologicalpopulation of the rumen increases.

[0005] Dosages given in U.S. Pat. No. 3,839,557 (in generalpropionate-increasing amounts) are in the range of from about 0.05 mg ofantibiotic per kg of body weight per day to about 2.5 mg/kg/day.

[0006] Administration methods given in U.S. Pat. No. 3,839,557 suggestincorporation of the antibiotic compound or compounds into tablets,drenches, boluses or capsules. There is disclosure that drenches of suchantibiotics can be prepared most easily by choosing a water soluble formof the antibiotic but that if an insoluble form is desired for somereason a suspension can be made. There is an indication that suspensionsof insoluble forms of the antibiotics can be prepared in non solventssuch as water but that suitable physiologically-acceptable adjuvants arenecessary in order to keep the antibiotics suspended. The adjuvants canbe chosen from amongst thickeners, surfactants, hydrophilicity agents,density affecting agents and surface tension affecting agents.

[0007] U.S. Pat. No. 3,839,557 suggests that a suspendible antibioticmay be offered as a dry mixture of the antibiotic in adjuvants to bediluted before use. A suggestion is made that such antibiotic can beincorporated into drinking water by adding a water soluble or watersuspendible form of the desired antibiotic to the water in a properamount. There is also disclosure that the method of administration ofthe antibiotic can be practised in combination with other treatments,ie. with other drugs used in combination.

[0008] European Patent Application 0139595 of Koffolk (1943) Limitedrelates to liquid feeds and milk replacers for ruminants andparticularly for suckling ruminants. Such compositions that aredisclosed contain ionophore antibiotics such as monensin, narasin,lasalocid (U.S. Pat. No. 3,715,372) and solinomycin.

[0009] In one form of the invention of EP 0139595 there is disclosed aliquid ionophore antibiotic composition for ruminants comprising anionophore antibiotic and at least one non toxic water miscible organicsolvent. The invention is also stated as providing a dry water solubleionophore antibiotic composition suitable for combination with anaqueous medium to form a liquid composition for ruminants, thecomposition comprising an ionophore antibiotic, a non toxic watermiscible organic solvent and a dry water soluble carrier therefor. Theinvention relates also to process for preparing liquid feeds whichinvolves dissolving such an ionophore antibiotic in a non toxic watersoluble organic solvent and admixing the resulting solution with aliquid feed, a water soluble vitamin concentrate or with drinking water.

[0010] The preferred ionophore antibiotics are those that have beensubjected to an extraction process whereby the antibiotic is no longerin the mycelial form, ie. is in a crystallisable form or a crystallineform.

[0011] Such compositions of EP 0139595 are stated as being liquid milkreplacers, or at least being capable of being incorporated in liquidfeeds or drinking water for administration to a suckling ruminant.

[0012] Example 13 of EP 0139595 refers to spraying in a horizontal mixerof a monensin solution (of the invention of EP 0139595 as defined) on adry milk replacer and then the subsequent “dissolving” thereof withwater.

DISCLOSURE OF INVENTION

[0013] The present invention relates to an alternative milk replacer ormilk extender composition to any of those disclosed and to relatedmethods.

[0014] In a first aspect the present invention consists in a drycomposition of an ionophore antibiotic capable of being suspended inwater directly to form a suspension (with or without any otheraddition(s)) deliverable into a ruminant (particularly a sucklingruminant) or, capable upon admixture with a dry milk powder and/or milksubstitute powder, of in turn then being mixed with water to form (withor without any other addition(s)) a suspension deliverable into aruminant (particularly a suckling ruminant) as a milk replacement orextender, said composition comprising, when expressed weight for weightwith respect to the overall dry composition,

[0015] from 10 to 95% (when expressed as the sodium salt) of at leastone crystalline ionophore antibiotic,

[0016] from 0 to 10% antifoam agent(s),

[0017] from 0.1 to 20% wetting and/or surfactant agent(s),

[0018] from 0.1 to 10% dispersal agent(s), and

[0019] from 0.1 to 20% suspension agent(s).

[0020] As used herein percentages of ionophore antibiotic refer to theantibiotic in any suitable form (eg. acid or salt) but expressed for thepurpose of the ranges by reference to its weight as the sodium salt asagainst the overall weight to the dry composition (where for the purposeof the overall weight the antibiotic is also accounted for by referenceto its weight as the sodium salt).

[0021] Preferably said antibiotic is from 90 to 95% w/w

[0022] Preferably said antifoam agents is from 0 to 2% w/w

[0023] Preferably said wetting/surfactant agents is from 0.1 to 5% w/w.

[0024] Preferably said dispersal agent is from 0.1 to 5% w/w

[0025] Preferably said suspension agent is from 0.1 to 5% w/w.

[0026] A preferred composition has

[0027] from 10 to 95% (eg. 10 to 80%) of at least one crystallineionophore antibiotic,

[0028] from 0.1 to 0.5% antifoam agent(s),

[0029] from 0.1 to 0.5% wetting and/or surfactant agent(s),

[0030] from 0.1 to 0.5% dispersal agent(s), and

[0031] from 0.1 to 0.5% suspension agent.

[0032] Preferably said ionophore antibiotic is selected from groupconsisting of Monensin, Lonomycin, lonomycin, Laidlomycin, Nigericin,Grisorixin, Dianemycin, Lenoremycin, Salinomycin, Narasin, AntibioticX206, Alborixin, Septamycin, Antibiotic A204, Maduramicin andSemduramicin, Compound 47224, Lasalocid (also including factors A, B, C,D and E), Mutalomycin, Isolasalocid A, Lysocellin, Tetronasin,Echeromycin, Antibiotic X-14766A, Antibiotic A23187, Antibiotic A32887,Compound 51532 and K41.

[0033] Preferably said ionophore antibiotic is Monensin.

[0034] Preferably said Monensin is Sodium Monensin.

[0035] Preferably said antifoaming agent is selected from the groupconsisting of Silicone antifoam powder such as Wacker ASP 3 hereinafterreferred to.

[0036] Preferably said wetting agent is selected from the groupconsisting of Sodium lauryl sulfate (anionic sulfates) such as CARSONOL™SLS-R (LONZA) or EMAL™ (POLEKAO).

[0037] Preferably said dispersal agent is selected from the groupconsisting of colloidal anhydrous silica such as Aerosil 200 ChemischeFabrik Kirsh Gmbtt.

[0038] Preferably said suspension agent(s) is or are selected from thegroup consisting of refined food grade galactomannan such as guar gum.

[0039] In a further aspect the present invention consists in the use ofa dry composition in accordance with the present invention afteradmixture with water to form a suspension as a feed supplement of asuckling or other ruminant.

[0040] Preferably said use involves milk powder or a milk substitutewhich is mixed into water either subsequently to, simultaneously with orprior to the suspension of the composition of the present invention insuch water.

[0041] The present invention also consists in, as a dry composition, adry composition in accordance with the present invention and a milkpowder and/or milk replacement powder.

[0042] In yet a further aspect the invention consists in a calf feedcomposition comprising a substantially homogeneous aqueous suspensionof, with respect to the composition volume,

[0043] (i) from 2 to 16 mg/L of a dry composition in accordance with thepresent invention,

[0044] (ii) optionally, a milk replacer composition, and

[0045] (iii) optionally, a milk extender composition.

[0046] Preferably from 5 to 30 g/L of a dry milk replacer compositionhas been included.

[0047] Preferably 10 to 25 g/L, eg. 15, or 20 g/L.

[0048] Preferably from 1 to 3 g/L milk extender (preferably about 2 g/L)is present or, preferably, is present in addition to a or the dry milkreplacer composition.

[0049] In yet a further aspect the invention consists in a drycomposition of monensin capable of being suspended in water directly toform a suspension (with or without any other addition(s)) deliverableinto a ruminant or, capable upon admixture with a dry milk powder and/ormilk substitute powder, of in turn then being mixed with water to form(with or without any other addition(s)) a suspension deliverable into aruminant as a milk replacement or extender, said composition comprising,when expressed weight for weight with respect to the overall drycomposition,

[0050] 95% (when expressed as the sodium salt), of crystalline sodiummonensin,

[0051] 19% silicone antifoam powder,

[0052] 3.5% sodium lauryl sulfate,

[0053] 2.5% colloidal anhydrous silica, and

[0054] 1.5% Guar gum.

[0055] In a still further aspect the invention consists in a calf feedcomposition comprising a substantially homogeneous aqueous suspensionof, with respect to the composition volume,

[0056] (I) from 2 to 16 mg/L of a composition comprising

[0057] 95% (when expressed as the sodium salt) of crystalline sodiummonensin,

[0058] 19% silicone antifoam powder,

[0059] 3.5% sodium lauryl sulfate,

[0060] 2.5% colloidal anhydrous silica, and

[0061] 1.5% Guar gum, AND

[0062] (II) 15 to 20 g/L of a milk replacer composition, and/or 1 to 3g/L of a milk extender composition.

[0063] In still a further aspect the invention consists in, as a premix.The components (i) and (ii), (i) and (iii) or (i), (ii) and (iii) for acalf feed composition as defined hereinbefore.

[0064] In still a further aspect the present invention consists in amethod of increasing feed conversion and growth rate of sucklingruminants which involves the administration orally or selfadministration orally of a composition of the present invention inconjunction with at least water into such ruminants.

[0065] Coccidiosis is a serious and common disease of dairy calves.During much of the time that dairy calves are at risk of coccidiosis,some or all or their diet comprises milk, milk replacers or milkextenders. The intake of these milk components is more consistent andcontrollable than other components of the diet. For this reason it isdesirable to be able to administer anti-coccidial agents to theseanimals in the milk portion of their diet.

[0066] Monensin sodium in prior art formulations does not remain evenlydistributed in milk, milk replacers or milk extenders for a sufficientperiod time to make it practical or safe for use in this manner.

[0067] A “milk extender” contains vitamins and minerals but in itself isnot a “milk replacer”.

[0068] Milk replacers are, as the name suggests, compositions capable ofreplacing the natural milk of the species. Typically a milk replacer ismade up from a skim milk powder (usually of the same species of mammal)plus a source of fat which can either be of animal or plant origin. Inthe case of cattle this fat replaces the normal cream in whole cowsmilk.

[0069] The present invention therefore envisages a calf feed tosupplement or replace the natural milk feed of an animal. The calf feedmay comprise

[0070] i) a milk replacer having an anti coccidial agent provided inaccordance with the present invention, substantially evenly distributedthere throughout

[0071] ii) a milk replacer and milk extender mixed/blended compositionitself including an anti coccidial agent (whether blended with the milkreplacer, the milk extender or both simultaneously).

[0072] Calves receive and ingest milk replacers and extenders within 24hours of preparation.

[0073] Monensin was selected as the ionophore antibiotic for detailedtrialing.

[0074] To ensure the safety of monensin wettable powder as a deliveryvector for ingestion as a liquid it was considered necessary thatmonensin, delivered as part of a calf feed eg. An aqueous composite as amilk replacer and/or milk extender, should remain evenly distributed for24 hours after homogeneous mixing with water.

[0075] The purpose of these trials was to determine the distributioncharacteristics of monensin wettable powder in aqueous preparations ofmilk replacers and milk extenders.

[0076] A preferred form of monensin wettable powder of the presentinvention having the formula as follows was used in the following trialsand assays.

[0077] MONENSIN (Sodium) WETTABLE POWDER

[0078] A preferred dry composition of an ionophore antibiotic (thisincludes a mixture of different types) comprises

[0079] 10 to 95% of at least one crystalline ionophore antibiotic (thepercentage being when the antibiotic is expressed as its sodium salt(eg. Monensin sodium whether or not it is in fact a monensin salt orindeed a sodium salt),

[0080] 0 to 2% antifoam agent(s),

[0081] 0.1 to 5% wetting and/or surfactant agent(s),

[0082] 0.1 to 5% dispersal agent(s), and

[0083] 0.1 to 5% suspension agent.

BRIEF DESCRIPTION OF DRAWINGS

[0084] A most preferred formulation and that trialed as describedhereinafter by reference to FIGS. 1 to 11 was prepared as now follows:

[0085] Blended in cube blender for 10 minutes, low speed: RUMENSIN ™Technical Elanco Animal Health  915 g (Monensin sodium) division of EliLilly Australia Pty Ltd, 112 Wharf Road, NSW 2114, Australia EL5167 (929gai/Kg) Silicone Antifoam Powder Wacker Silicone  10 g ASP3 availablefrom Amcor Trading, PO Box 33 Drumoyne NSW 2047 Australia EMAL ™10NEEDLE  35 g sodium lauryl sulfate PT Polekao Indonesia Chemicalsavailable in Australia from P&M O'Brien Trading Pty Ltd, ACN 054787161(Lot No.1410) AEROSIL 200 ™ Chemische Fabrik Kirsh  25 g (colloidalanhydrous silica) GmbH Product Code HH01 available in Australia fromChemical Distributors Fax 61 2 9385867 Guar gum Woods or Woods Pty Ltd 15 WW 250 F ACN 001 092 066 (galactomannan E412) Australia 1000 g

[0086] Monensin sodium wettable powder was formulated this to enablemonensin to remain evenly distributed in aqueous calf feed compositionsfor a period of 24 hours.

[0087] Calf Feed Components of Trials: Milk Replacer VEANAVITE ™ InstantCalf Milk replacer 13426 - available from Philip Grant, PO Box 160,Cowra, NSW 2794, Australia. Milk Extenders PREMAXT ™ Calf Booster[available from Ridley Agriproucts Pty Ltd 39 Oxford Street, Epping, NSW2121, Australia.] CALFGO ™ (Rhone Poulenc) B/N 55654 [available fromRhone Poulenc Animal Nutrition 19-25 Paramount Road, West Footscray,Victoria 3012, Australia.] Monensin (sodium) - MONENSIN (sodium)(RUMENSIN ™) WETTABLE POWDER (B/N 470 Assay No. 950103 (86.7%)) of thepresent invention ie. The blend resulting from the immediately precedingformulation. Water —

COW'S MILK STANDARD

[0088] The wettable powder of the present invention was developed foruse in milk replacers which may additionally include milk extenders. Itis the suspendability of the wettable powder in such aqueouscompositions of milk replacers additionally enhanced where desired bymilk extenders, that is of importance. For this reason therefore thesuspendability of monensin wettable powder in water was not considered auseful standard as both milk and milk replacer based aqueouscompositions are much more complex liquids than mere water particularlyin regard to the fat, sugar, and protein present. It was thereforeconsidered that for the purpose of assaying for the strengths ofmonensin during the trials an appropriate standard for comparativepurposes (the assay for monensin) was a known strength composition ofmonensin sodium in whole cows milk.

[0089] First a known strength (8000 mg/L) crystalline monensin sodiumsolution in methanol was prepared. This was then used to formulate theassay standard formulations (the methanol having been evaporated by astream of nitrogen) after pipetting of amounts of the monensin/methanolinto 2 liter volumetric flasks as follows: Monensin concentration inmilk (mg/L) (as expressed as (mL) of the Whole Cows Monensin and not thesalt) monensin/methanol solution Milk (L) 2 0.5 2 6 1.5 2 8 2.0 2 12 3.02 16 4.0 2

[0090] The monensin in milk concentrations were achieved by the additionof cow's milk into the volumetric flask.

[0091] IN MILK REPLACERS WITH MILK EXTENDERS

[0092] It is anticipated that for commercial use monensin wettablepowder will be added to aqueous calf feed compositions (milk replacersoptionally with milk extenders) at a rate of 6 mg/L monensin. Theaddition rates of monensin used in this trial were chosen to represent arange around this anticipated use rate (ie. 2, 6, 8, 12, 16 mg/L).

[0093] For the purpose of the trials the milk replacer used wasVEANAVITE™ instant calf milk replacer identified above.

[0094] Two formulations of milk extender (Formulations 1 and II) wereexamined in this trial. Both formulations are of commercial milkextenders currently used in the Australian market. Per kg [PREMAX ™ CalfBooster] Milk Extender Formulation I Retinyl acetate (vitamin A) 186,000IU Cholecalciferon (vitamin D₃) 18,000 IU di-alpha-tocopheryl acetate(vitamin E) 1.86 g Thiamine hydrochloride 400 mg Pyridoxinehydrochloride 150 mg Cyanocobalamin 20 mg Biotin 3.0 mg Folic acid 8.0mg Menadione 65.0 mg Nicotinic acid 696.0 mg D-calcium pantothenate262.0 mg Choline 67.86 mg Selenium (Se) 1.0 mg Cobalt (Co) 3.0 mg Iodine(I) 15.0 mg Copper (Cu) 292.0 mg Manganese (Mn) 749.0 mg Zinc (Zn) 900.0mg Ferrous iron (Fe++) 1.13 g Lysine 2.00 g di-Methlonine 2.00 gMagnesium (Mg) 469.97 g Maximum fluorine (F) Nil Carrier Prebase ™ ?[CALGRO ™] Milk Extender Formulation II Vitamin A 40,000 IU Vitamin D6,000 Vitamin E 80 mg Vitamin K 2 mg Thiamine (B1) 6 mg Riboflavin (B2)7 mg Pyridoine (B6) 4 mg Niacin 20 mg B12 0.05 mg Biotin 1 mg Vitamin C100 mg Pantothenic acid 13 mg Folic acid 0.006 mg Choline Chloride 200mg Magnesium 300 mg Copper 10 mg Cobalt 0.8 mg Zinc 70 mg Iron 150 mgIodine 0.8 mg Selenium 0.2 mg Manganese 50 mg Molybdenum 4 mg Avoparcin40 mg

[0095] Calf feed formulations trialled were prepared with water with 15g/L and 20 g/L VEANAVITE™ Instant Milk replacer and either 2 g/L PremaxCalf Booster or 2 g/L Calfgro.

[0096] 15 g/L milk replacer/2 g/L extender formulations were studied atMonensin sodium concentrations of 2 mg/L, 6 mg/L, 8 mg/L, 12 mg/L and 16mg/L.

[0097] 20 g/L milk replacers/2 g/L extender formulations were studied ata Monensin sodium concentration of 6 mg/L.

[0098] Each monensin wettable powder spiked formulation was sampled atthe top and bottom of the prepared volume at 0, 1, 3, 5 and 24 hours.Sample extraction was performed immediately and extracts analysed thesame day.

[0099] ANALYSES

[0100] (i). Pipette two 40 mL portions for zero time analysis.

[0101] (ii). At subsequent time points pipette a 40 mL portion from 2.5cm under the surface (top sample) and 1.5 cm above the container bottom(bottom sample).

[0102] (iii). Prepare extracts for HPLC analysis on each 40 mL portionas they are sampled.

[0103] (iv). Analysis by HPLC. Monensin is extracted from various milkformulations with dichloromethane and is quantified using a highperformance liquid chromatograph (LC) equipped with a post columnreactor. Monensin is acid—reacted with vanillin, and the resultingproducts are measured by a variable wavelength visible detectoroperating at 520 nm. The method is based on the Lilly ResearchLaboratories method AM-AA-CR-R150-AB-791.

[0104] Milk replacer was prepared at 15 and 20 g/L concentrations sincethe concentration of milk replacer received by calves is usually variedwith the age of the calf.

[0105] RESULTS TABLE 1 Suspension in water of monensin wettable powderwith 15 g/L milk replacer and 2 g/L milk extender samples Theoretical mgmg monensin monensin Position 0 Hr 1 Hr 3 Hr 5 Hr 24 Hr 2 mg/L Extender1 Top 1.9 1.9 1.8 1.9 2.0 Bottom — 1.9 1.8 1.8 2.1 Extender 2 Top 1.91.8 1.8 1.8 2.0 Bottom — 1.8 1.9 1.8 2.0 6mg/L Extender 1 Top 6.0 5.96.0 5.2 5.7 Bottom — 6.0 5.7 5.8 5.8 Extender 2 Top 6.3 6.2 6.1 6.1 6.1Bottom — 5.8 5.7 5.7 6.1 8 mg/L Extender 1 Top 8.0 7.4 6.9 7.2 7.4Bottom — 7.3 7.0 7.0 7.2 Extender 2 Top 8.0 8.1 8.4 8.0 7.6 Bottom — 7.77.7 7.6 7.9 12 mg/L Extender 1 Top 12.5 12.2 12.3 12.5 11.9 Bottom —12.0 12.1 12.0 13.0 Extender2 Top 12.4 11.9 11.3 11.7 11.3 Bottom — 12.011.6 11.5 11.8 16 mg/L Extender 1 Top 16.6 16.7 16.4 16.0 17.1 Bottom —16.3 16.5 16.0 16.2 Extender 2 Top 16.7 16.2 16.1 16.0 15.6 Bottom —16.2 16.1 15.6 15.8

[0106] TABLE 2 Suspension in water of Monensin wettable powder with 20g/L milk replacer and 2g/L milk extender Spike Position 0 Hr 1 Hr 3 Hr 5Hr 24 Hr 6 mg/L Extender 1 Top 6.0 5.9 5.8 5.7 5.9 Bottom — 5.6 5.6 5.55.5 Extender 2 Top 6.0 5.6 5.6 5.7 5.6 Bottom — 5.7 5.6 5.5 5.4

[0107] Monensin wettable powder remained evenly distributed in the 15g/L milk replacer solution at all concentrations of monensin for 24hours after preparation. Please see FIGS. 1 to 10.

[0108] Monensin wettable powder remained evenly distributed in the 20g/L milk replacer at 6 mg/L for 24 hours after preparation. Please seeFIGS. 10, 11A and 11B.

[0109] MIXING and APPLICATION

[0110] A quantity of dry components whether mixed in togethersimultaneously or in any sequence is capable of easy blending in a cubeblender requiring only about 10 minutes low speed blending. Mixture isthen passed through a hammer mill to form a powder.

[0111] Such a powder can then be blended with a dry milk powder or milkreplacement powder and subsequently as required then be suspended alongwith the milk powder or milk replacement powder in water for deliveryinto the animal.

[0112] Alternatively the composition can be directly suspended intowater and if desired sprayed onto milk powder and then eitherimmediately or subsequently that milk powder (or milk replacement powderor a mixture of both) can as required then be made up with additionalwater to provide the feed supplement for the animal including theionophore antibiotic delivered by a composition of the presentinvention.

[0113] Other methods of administration include separate suspension ofthe composition of the present invention in water and the suspension ofmilk powder or a milk powder substitute in water and then the bringingof the two suspensions together prior to delivery into the animal. Theycan if desired be serially administered to the animal.

[0114] COMMENT

[0115] A composition in accordance with the present invention hasadvantages over any foreshadowed in the aforementioned U.S. Pat. No.Specification 3,839,557 in that it allows delivery of the antibiotic toyoung suckling ruminants as part of their milk diet by incorporation inthe milk replacer powder during manufacture or at mixing of the milkreplacer with water. This is more practical than dosing with a tablet,drenching or adding to water and over any disclosed in EP 0139595 inthat no organic solvent for the ionophore antibiotic is a prerequisite.EP 0139595 discloses no example of a composition not requiring anorganic solvent.

[0116] An omission of an organic solvent as a precursor to suspension inwater of the antibiotic has several advantages

[0117] Monensin has poor solubility in all organic solvents exceptmethyl alcohol (a poison to mammals) and n-propyl alcohol - when thesesolutions are added to water monensin crystallises out of solution

[0118] other features—non flammable

[0119] no odour

[0120] no separation problems (as above)

[0121] cost effective

[0122] simple manufacturing process

[0123] high concentration of active monensin

[0124] easily mixed with powders, water and can be sprayed

[0125] better stability in a powder form.

1. A dry composition of an ionophore antibiotic capable of beingsuspended in water directly to form a suspension (with or without anyother addition(s)) deliverable into a ruminant or, capable uponadmixture with a dry milk powder and/or milk substitute powder, of inturn then being mixed with water to form (with or without any otheraddition(s)) a suspension deliverable into a ruminant as a milkreplacement or extender, said composition comprising, when expressedweight for weight with respect to the overall dry composition, from 10to 95% (when expressed as the sodium salt) of at least one crystallineionophore antibiotic, from 0 to 10% antifoam agent(s), from 0.1 to 20%wetting and/or surfactant agent(s), from 0.1 to 10% dispersal agent(s),and from 0.1 to 20% suspension agent(s).
 2. A composition of claim 1wherein said antibiotic (when expressed as the sodium salt) is from 90to 95% w/w.
 3. A composition of claim 1 wherein said antifoam agent(s)is from 0 to 2% w/w.
 4. A composition of claim 1 wherein saidwetting/surfactant agents is from 0 to 5% w/w.
 5. A composition of claim1 wherein said dispersal agent is from 0.1 to 5% w/w.
 6. A compositionof claim 1 wherein said suspension agent is from 0.1 to 5% w/w.
 7. Acomposition of claim 1 comprising from 10 to 95% (when expressed as thesodium salt) of at least one crystalline ionophore antibiotic, from 0.1to 0.5% antifoam agent(s), from 0.1 to 0.5% wetting and/or surfactantagent(s), from 0.1 to 0.5% dispersal agent(s), and from 0.1 to 0.5%suspension agent.
 8. A composition of any one of the preceding claimswherein said ionophore antibiotic is selected from group consisting ofMonensin, Lonomycin, lonomycin, Laidlomycin, Nigericin, Grisorixin,Dianemycin, Lenoremycin, Salinomycin, Narasin, Antibiotic X206,Alborixin, Septamycin, Antibiotic A204, Maduramicin and Semduramicin,Compound 47224, Lasalocid (also including factors A, B, C, D and E),Mutalomycin, Isolasalocid A, Lysocellin, Tetronasin, Echeromycin,Antibiotic X-14766A, Antibiotic A23187, Antibiotic A32887, Compound51532 and K41.
 9. A composition of claim 8 wherein said ionophoreantibiotic is monensin in the acid or a salt form.
 10. A composition ofclaim 9 wherein said monensin is included in the form of sodium monensm.11. A composition of claim 1 or 3 wherein said antifoaming agent(s) isor includes silicone antifoam powder.
 12. A composition of claim 1wherein said wetting agent(s) is or includes an anionoic sulfate.
 13. Acomposition of claim 12 wherein said anionic sulfate is sodium laurylsulfate.
 14. A composition of claim 1 or 5 wherein said dispersalagent(s) is or includes a colloidal anhydrous silica.
 15. A compositionof claim 1 or 6 wherein said suspension agent(s) is or includes agalactomannan.
 16. A composition of claim 15 wherein said suspensionagent(s) is guar gum.
 17. The use of a dry composition in accordancewith any one of the preceding claims after admixture with (at least)water to form a suspension as a feed supplement of a suckling or otherruminant.
 18. The use of claim 17 further involving milk powder or amilk substitute which is mixed into water either subsequently to,simultaneously with or prior to the suspension of the composition of thepresent invention in such water.
 19. As a dry composition, a drycomposition in accordance with any one of claims 1 to 16 and a milkpowder and/or milk replacement powder.
 20. A calf feed compositioncomprising a substantially homogeneous aqueous suspension of, withrespect to the composition volume, (i) from 2 to 16 mg/L of a drycomposition as claimed in any one of claims 1 to 16, (ii) optionally, amilk replacer composition, and (iii) optionally, a milk extendercomposition.
 21. A composition of claim 20 wherein from 5 to 30 g/L of adry milk replacer composition has been included.
 22. A composition ofclaim 20 wherein from 15 to 20 g/L of dry milk replacer composition hasbeen included.
 23. A composition of any one of claims 20 to 22 whereinfrom 1 to 3 g/L of dry milk extender has been included.
 24. Acomposition of claim 23 wherein about 2g/L of milk extender has beenincluded.
 25. As a premix, the dry components of (i) and (ii), (i) and(iii) or (i), (ii) and (iii) of and suitable for a calf feed compositionas defined in any one of claims 20 to
 24. 26. A method of increasingfeed conversion and growth rate of suckling ruminants which involves theadministration orally or self administration orally of a composition ofany one of claims 1 to 16 in conjunction with at least water into suchruminants or a composition of any one of claims 20 to 24 into suchruminants.
 27. A dry composition of monensin capable of being suspendedin water directly to form a suspension (with or without any otheraddition(s)) deliverable into a ruminant or, capable upon admixture witha dry milk powder and/or milk substitute powder, of in turn then beingmixed with water to form (with or without any other addition(s)) asuspension deliverable into a ruminant as a milk replacement orextender, said composition comprising, when expressed weight for weightwith respect to the overall dry composition, 95% (when expressed as thesodium salt), of crystalline sodium monensin, 19% silicone antifoampowder, 3.5% sodium lauryl sulfate, 2.5% colloidal anhydrous silica, and1.5% Guar gum.
 28. A calf feed composition comprising a substantiallyhomogeneous aqueous suspension of, with respect to the compositionvolume, (I) from 2 to 16 mg/L of a composition comprising 95% (whenexpressed as the sodium salt) of crystalline sodium monensin, 19%silicone antifoam powder, 3.5% sodium lauryl sulfate, 2.5% colloidalanhydrous silica, and 1.5% Guar gum, AND (II) 15 to 20 g/L of a milkreplacer composition, and/or 1 to 3 g/L of a milk extender composition.